| abstract |
Cancer specific splicing events in the Wnt/β-catenin signaling pathway are associated with progression of myelogenous leukemia. Misspliced genes of interest include GSK3β. In some embodiments of the invention, polynucleotides are provided that correspond to misspliced GSK3β transcripts associated with cancer. Such transcripts are characterized by a deletion of exon (8), and particularly in exon (8) and (9). Detection of such transcripts in cells is indicative of the presence of leukemia, and particularly of the presence of leukemia stem cells. In other embodiments, polypeptides are provided that are encoded by misspliced GSK3β transcripts associated with cancer. Such polypeptides are useful as diagnostic markers for cancer, and as a target for screening of therapeutic agents. Animal models comprising a human LSC having a misspliced GSK3b transcript provide a useful model for leukemia, for drug/gene screening in the prevention and treatment of leukemia in humans, etc. |